title: Lentiviral-mediated p38 MAPK RNAi attenuates aldosterone-induced myocyte apoptosis.
abstract: Aldosterone-induced myocyte apoptosis is an important component of cardiovascular disease. While the p38 mitogen-activated protein kinase (p38 MAPK) pathway has been shown to be crucial in myocyte apoptosis, whether aldosterone induces myocyte apoptosis through this pathway remains unclear. In the present study, three individual strands of p38 MAPK short hairpin RNA (ShRNA), delivered by lentiviral vectors (PGLV), were constructed and used to explore the role of p38 MAPK pathway activation in aldosterone-mediated myocyte apoptosis in cultured myocytes and normotensive rats. Aldosterone stimulation increased myocyte apoptosis, caspase-3 expression levels and p38 MAPK mRNA and protein expression levels in vitro and in vivo. PGLV-ShRNA3 transduction decreased aldosterone-mediated myocyte apoptosis and p38 MAPK mRNA and protein expression levels in vitro (all P<0.01). PGLV-ShRNA3 transduction significantly decreased aldosterone-mediated myocyte apoptosis, p38 MAPK mRNA and protein expression levels in normotensive rats (P<0.01, P<0.01 and P<0.05, respectively). Results from the present study suggest that aldosterone directly induces myocyte apoptosis through the p38 MAPK pathway and the gene silencing of p38 MAPK may protect cardiac myocytes from aldosterone-mediated apoptosis.
authors.affiliation: Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Liang
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Qizhu
authors.initials: Q
authors.lastname: Tang
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D014161:Transduction, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000450:Aldosterone; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3